Key result
Anti-ANGPTL3/IL22 fusion protein reduces UACR and alleviates renal damage in mice with nephropathy.
Why the study?
Nephrotic syndrome treatment relies on immunosuppressants with numerous side effects, creating an urgent need for effective and safe alternative therapies.
Does a bifunctional anti-ANGPTL3/IL22 fusion protein improve renal function and pathology in mice with adriamycin-induced nephropathy?
Does a bifunctional anti-ANGPTL3/IL22 fusion protein improve renal function and pathology in mice with adriamycin-induced nephropathy?
A novel anti-ANGPTL3/IL22 fusion protein demonstrates therapeutic potential for nephrotic syndrome in a mouse model by preserving mitochondrial integrity and reducing apoptosis.
Does not support clinical use in nephropathy; leaves open translation of ANGPTL3/IL-22 fusion proteins to human trials.
Nephrotic syndrome (NS) is a major cause of end-stage renal disease. Treating NS relies on immunosuppressants, which have numerous side effects. Therefore, there is an urgent need to identify effective and safe alternative treatments for NS. Angiopoietin-like protein 3 (ANGPTL3) exacerbates proteinuria, whereas interleukin (IL)-22 has a reparative effect on renal cells. In the present study, we developed a bifunctional anti-ANGPTL3/IL22 fusion protein and validated its efficacy in an adriamycin-induced nephropathy in mice. The fusion protein significantly decreased the urinary albumin-to-creatinine ratio, serum creatinine, blood urea nitrogen, and total cholesterol levels while increasing serum albumin levels. Pathological renal damage was also alleviated. These therapeutic effects were accompanied by the preservation of mitochondrial integrity, reduced apoptosis, and inhibited autophagy. Finally,We humanized the fusion protein to facilitate its potential clinical translation. In conclusion, our results revealed that the anti-ANGPTL3/IL22 bifunctional fusion protein ameliorates NS by protecting mitochondria, inhibiting apoptosis and suppressing autophagy, highlighting a novel therapeutic approach for NS.
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Ma et al. (2026) studied Nephrotic syndrome (adriamycin-induced nephropathy). Bifunctional anti-ANGPTL3/IL22 fusion protein was evaluated on Urinary albumin-to-creatinine ratio, serum creatinine, blood urea nitrogen, total cholesterol, and serum albumin levels. A bifunctional anti-ANGPTL3/IL22 fusion protein significantly decreased urinary albumin-to-creatinine ratio, serum creatinine, and BUN, and alleviated renal damage in mice with nephropathy.
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